Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous work in neuronal cultures has shown that several antagonists of P2 ATP receptors prevent cell death evoked by hypoglycaemia, chemical hypoxia, mitochondria dysfunction, as well as glutamate-dependent excitotoxicity and low potassium-induced apoptosis. Experiments are now designed to examine which biological pathway contributes to cell death/survival under glucose starvation. We show here that, consequently to hypoglycaemic insults, cerebellar granule neurones undergo a combination of apoptosis and necrosis both inhibited by the P2 receptor antagonist basilen blue. This is demonstrated by morphological and biochemical features, such as TdT-mediated dUTP-biotin nick end-labelling, fluorescent staining of nuclear chromatin using Hoechst 33258, direct counting of intact viable nuclei and extracellular releasing of the cytosolic enzyme LDH. Furthermore, we show that hypoglycaemia induces outflow of cytochrome c from mitochondria and it up-regulates heat-shock proteins HSP70, but not HSP90, glucose-regulated proteins GRP75 and GRP78, as well as expression and activity of the enzyme caspase-2. Basilen blue can modulate only some of these effects. Our data contribute to dissect the role played by P2 receptor antagonism in sustaining neuroprotection against metabolic stresses.
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PMID:Hypoglycaemia-induced cell death: features of neuroprotection by the P2 receptor antagonist basilen blue. 1109 77

The contamination of water by metal compounds is a worldwide environmental problem. This study was undertaken to evaluate the impact of short-term cadmium exposure on metabolic patterns of the freshwater fish Oreochromis niloticus. The fish were exposed to 320, 640, 1,280 and 2,560 microg/l sublethal concentrations of Cd++ (CdCl2) in water for 7 days. The specific activities of the enzymes phosphofructo kinase (PFK-E.C.2.7.1.11.), lactate dehydrogenase (LDH-E.C.1.1.1.27.) and creatine kinase (CKE.C.2.7.3.2.) were decreased in white muscle after cadmium treatments, indicating decreases in the capacity of glycolysis in this tissue. Cadmium exposure induced increased glucose concentration in white muscle of fish. On the other hand, cadmium exposure at sublethal concentrations increased phosphofructo kinase and LDH in red muscle of fish. Cadmium significantly decreased total protein concentrations in liver and white muscle regardless of tissue glycogen levels. The data suggest that cadmium acts as a stressor, leading to metabolic alterations similar to those observed in starvation.
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PMID:Environmental cadium exposure and metabolic responses of the Nile tilapia, Oreochromis niloticus. 1150 39

Glucose-regulated proteins 75(grp75) is a member of hsp70 family. The expression of grp75 is upregulated during glucose starvation (such as ischemia). To evaluate grp75 function, CHL cells were cultured with glucose-free media for 20 h (A) and glucose-free media for 12 h + glucose-containing media for 8 h (ischemia reperfusion) (B). A constructed rat grp75 cDNA expression vector (pcDNA/grp75) was transfected into CHL cells and a cell strain that stably overexpressed grp75 was obtained. The transfected cells and untransfected cells(control group) were cultured with A or B. By MTT, LDH leakage measurement and flow cytometry analysis, growth rate of untransfected cells in B is significantly lower than that in glucose-containing media for 20 h (C) (p < 0.05) and A (p < 0.05). Growth rate of transfected cells is apparently higher than that of control group in B (p < 0.01). LDH liberation percentage of untransfected cells in B is obviously higher than that in C(p < 0.01) and it is not different from A(p > 0.05). LDH liberation percentage of transfected cells is apparently lower than that of control group in B(p < 0.01). Apoptosis of transfected cells is obviously lower by flow cytometry analysis. These results provide evidence for the cytoprotective function of grp75 during glucose starving and ischemia reperfusion.
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PMID:[Molecular chaperone GRP75 reprove cells from injury caused by glucose deprivation]. 1472 51

Ras proteins exert a pivotal regulatory function in signal transduction involved in cell proliferation and their activation mutation leads to malignant cell transformation. However, the role of Ras proteins in autophagy, an intracellular protein degradation process in cell growth control is unknown. In the present study, we demonstrate that the degradation of long-lived proteins in NIH3T3 cells in response to nutrient starvation was significantly suppressed by oncogenic RasVal12 transformation in a rapamycin (mTOR inhibitor)-sensitive manner. Morphologic observations also show the decrease in the formation of autophagic vacuoles upon the Ras transformation. Furthermore, epidermal growth factor or serum downregulated the protein degradation induced by serum starvation and the dominant-negative RasAsn17 mutant counteracted this suppressive effect, indicating that Ras mediates the growth factor downregulation of autophagy. The suppression of protein degradation by the activated RasVal12 was mediated by the class I phosphatidyl inositol 3-kinase (PI3-kinase), but not either or Raf Ral GDS. Consistent with this, RasVal12 and class I PI3-kinase inhibited the rate of autophagic sequestration of LDH. These data suggest that Ras plays a critical role as a negative regulator for nutrient deprivation-induced autophagy through the class I PI3-kinase signaling pathway.
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PMID:Ras is involved in the negative control of autophagy through the class I PI3-kinase. 1506 41

The current study examined specific bioenergetic markers associated with the metabolic phenotype of several human and mouse glioma cell lines. Based on preliminary studies, we hypothesized that glioma cells would express one of at least two different metabolic phenotypes, possibly acquired through progression. The D-54MG and GL261 glioma cell lines displayed an oxidative phosphorylation (OXPHOS)-dependent phenotype, characterized by extremely long survival under glucose starvation, and low tolerance to poisoning of the electron transport chain (ETC). Alternatively, U-251MG and U-87MG glioma cells exhibited a glycolytic-dependent phenotype with functional OXPHOS. These cells displayed low tolerance to glucose starvation and were resistant to a ETC blocker. Moreover, these cells could be rescued in low glucose conditions by oxidative substrates (e.g., lactate, pyruvate). Finally, these two phenotypes could be distinguished by the differential expression of LDH isoforms. OXPHOS-dependent cells expressed both LDH-A and -B isoforms whereas glycolytic-dependent glioma cells expressed only LDH-B. In the latter case, LDH-B would be expected to be essential for the use of extracellular lactate to fuel cell activities. These observations raise the possibility that the heterogeneity in glucose metabolism and, in particular, the sole expression of LDH-B, might identify an important biological marker of glioma cells that is critical for their progression and that might afford a new target for anticancer drugs.
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PMID:Glucose metabolism heterogeneity in human and mouse malignant glioma cell lines. 1619 82

Platinum resistance of cancer cells may evolve due to a decrease in intracellular drug accumulation, decreased cell permeability or by an increased deactivation of the drug by glutathione (GSH). The aim of this study was (1) to investigate the effect of adenosine 5'-triphosphate (ATP) on the cytotoxicity of cisplatin in a large cell lung carcinoma cell line (H460), and (2) to examine the potential involvement of increased cisplatin uptake, GSH depletion and pyrimidine starvation by ATP in this effect. H460 cells were harvested and seeded (5% CO(2); 37 degrees C). Subsequently, cells were incubated with medium or ATP followed by an incubation with cisplatin. Cytotoxicity screening was analyzed by the sulforhodamine B (SRB) colorimetric assay, lactate dehydrogenase and caspase-3/7 activity. Pre-incubation for 72h with 0.3 and 3mM ATP strongly enhanced the anti-proliferative potency of cisplatin 2.9- and 7.6-fold, respectively. Moreover, after incubation of H460 cells with 0.3mM ATP the intracellular platinum concentration increased, indicating increased cisplatin uptake by ATP. ATP, despite lowering the LD(50) of cisplatin, did not modulate GSH levels in H460 cells. ATP itself showed a biphasic effect on H460 cell growth: 0.3mM inhibited H460 cell growth via the pyrimidine starvation effect, activation of caspase-3/7 and LDH leakage, while 3mM ATP showed no effect on cell growth. In conclusion, ATP sensitizes the H460 cells to cisplatin-induced apoptosis. The effect of 0.3mM ATP is not due to GSH depletion but involves increased cisplatin uptake and pyrimidine starvation due to ATP conversion to adenosine followed by cellular uptake.
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PMID:ATP sensitizes H460 lung carcinoma cells to cisplatin-induced apoptosis. 2015 29

Clinical use of doxorubicin (DOX) is limited by its cardiotoxic side effects. Recent studies established that metformin (MET), an oral antidiabetic drug, possesses an antioxidant activity. However, whether it can protect against DOX-induced energy starvation and mitochondrial damage has not been reported. Our results, in a rat model of DOX-induced cardiotoxicity, show that DOX treatment significantly increased serum levels of LDH and CK-MB, indicators of cardiac injury, and induced expression of hypertrophic gene markers. DOX also caused marked decreases in the cardiac levels of glutathione, CoA-SH and ATP, and mRNA expression of catalase and NQO-1. These biochemical changes were associated with myocardial histopathological and ultrastructural deteriorations, as observed by light and electron microscopy, respectively. Cotreatment with MET (500 mg/kg) eliminated all DOX-induced biochemical, histopathological, and ultrastructural changes. These findings demonstrate that MET successfully prevents DOX-induced cardiotoxicity in vivo by inhibiting DOX-induced oxidative stress, energy starvation, and depletion of intramitochondrial CoA-SH.
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PMID:Metformin rescues the myocardium from doxorubicin-induced energy starvation and mitochondrial damage in rats. 2266 20

Fibroblasts could be considered as connective tissue cells that are morphologically heterogeneous with diverse functions depending on their location and activity. These cells play critical role in health and disease such as cancer and wound by Production of collagen, fibronectin, cytokines and growth factors. Absence of insulin and other growth factors in serum deprivation condition and similarity of this condition to the environment of tumor cells and ulcer made us to investigate anaerobic glycolysis in these cells. To this end, we cultured fibroblasts isolated from fresh human newborn foreskin in serum free medium for 16, 24, 48 and 72 hrs and measured glucose consumption, lactate secretion and intracellular LDH in these cells. The results showed despite the lack of insulin, the 16hr serum starved fibroblasts consumed glucose similar to non-starved fibroblasts control. Moreover, in this condition these cells secreted higher levels of lactate and exhibited higher levels of intracellular LDH in comparison to non-starved fibroblasts control. Thus it could be concluded that in serum starvation condition, the newborn human dermal fibroblasts may change the metabolic strategy to Warburg effect. This finding opens a new perspective to further understanding the basic mechanisms involved in communication between tumor cells and fibroblasts.
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PMID:Human fibroblast switches to anaerobic metabolic pathway in response to serum starvation: a mimic of warburg effect. 2503 56

Seasonal plasticity in the small intestine of neonatal tegu lizards was investigated using morphometry and analysis of enzymes involved in supplying energy to the intestinal tissue. In the autumn, the intestinal mass (Mi) was 1.0% of body mass and the scaling exponent b=0.92 indicated that Mi was larger in smaller neonates. During arousal from dormancy Mi was 23% smaller; later in spring, Mi increased 60% in relation to the autumn and the exponent b=0.14 indicated that the recovery was disproportionate in smaller tegus. During the autumn, the intestinal villi were greatly elongated; by midwinter, the Hv, SvEp, and VvEp were smaller than during the autumn (59%, 54%, 29%) and were restored to autumn levels during spring. In the active tegus, the maximum activity (Vmax) of enzymes indicated that the enterocytes can obtain energy from different sources, and possess gluconeogenic capacity. During winter, the Vmax of CS, HOAD, GDH, PEPCK was 40-50% lower in relation to the autumn and spring, while the Vmax of HK, PK, LDH, AST was unchanged. The hypoglycemia and the mucosal atrophy/ischemia during winter would prevent the enterocytes from using glucose, whereas they could slowly oxidize fatty acids released from body stores and amino acids from the tissue proteolysis to satisfy their needs of energy. Contrastingly, starvation during spring caused severe mass loss (50%); the tissue protein and the VvEp and VvLP did not change while the thickness of the muscular layer increased 51%, which suggested different effects along the length of the organ. In addition, the Vmax of the glycolytic enzymes was lower, indicating that a regulatory mechanism would spare blood glucose for vital organs during unanticipated food restriction.
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PMID:Morphological and metabolic adjustments in the small intestine to energy demands of growth, storage, and fasting in the first annual cycle of a hibernating lizard (Tupinambis merianae). 2687 95

Maintenance of an intact epithelial barrier constitutes a pivotal defense mechanism against infections. Staphylococcus aureus is a versatile pathogen that produces multiple factors including exotoxins that promote tissue alterations. The aim of the present study is to investigate the cytopathic effect of staphylococcal exotoxins SEA, SEG, SEI, SElM, SElN and SElO on the cell cycle of various human cell lines. Among all tested exotoxins only SEIO inhibited the proliferation of a broad panel of human tumor cell lines in vitro. Evaluation of a LDH release and a DNA fragmentation of host cells exposed to SEIO revealed that the toxin does not induce necrosis or apoptosis. Analysis of the DNA content of tumor cells synchronized by serum starvation after exposure to SEIO showed G0/G1 cell cycle delay. The cell cycle modulating feature of SEIO was confirmed by the flow cytometry analysis of synchronized cells exposed to supernatants of isogenic S. aureus strains wherein only supernatant of the SElO producing strain induced G0/G1 phase delay. The results of yeast-two-hybrid analysis indicated that SEIO's potential partner is cullin-3, involved in the transition from G1 to S phase. In conclusion, we provide evidence that SEIO inhibits cell proliferation without inducing cell death, by delaying host cell entry into the G0/G1 phase of the cell cycle. We speculate that this unique cell cycle modulating feature allows SEIO producing bacteria to gain advantage by arresting the cell cycle of target cells as part of a broader invasive strategy.
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PMID:Staphylococcal Enterotoxin O Exhibits Cell Cycle Modulating Activity. 2714 68


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